18-OR

Abstract

Objectives While obesity is a major risk factor for preeclampsia, which is new-onset hypertension in pregnancy, the mechanisms linking obesity and hypertension during preeclampsia are not understood. Hypertension in preeclampsia is associated with placental ischemia-induced release of factors such as anti-angiogenic sFlt-1 into the maternal circulation which antagonizes vascular endothelial growth factor (VEGF) and promotes endothelial dysfunction. The purpose of this study was to determine the effect of obesity on angiogenic factors and endothelial function in obese melanocortin 4 receptor (MC4R) knockout rats (MC4R+/−, n = 4–9) and lean control MC4R+/+ rats ( n = 4–8). Methods EchoMRI for measuring total body fat mass; carotid arterial catheters for measuring mean arterial blood pressure; ELISAs; wire myography. Results At gestational day (GD) 18, body weight (362 ± 6 vs. 336 ± 5 g) and total body fat mass (62 ± 6 vs. 45 ± 5 g) were greater ( P P P P Conclusions These data indicate that during normal pregnancy, obesity is associated with greater circulating VEGF levels and nitric oxide-dependent vasorelaxation in resistance arteries. Because soluble factors from the ischemic placental target reduce nitric oxide bioavailability, we propose that the hypertensive and endothelial dysfunction responses to reductions in uterine perfusion may be exaggerated in obese pregnant animals. Funding: HL105324, HL51971. Disclosures F.T. Spradley: None. A.C. Palei: None. J.P. Granger: None.